Candidate Review:

The Influence of GABA Metabolism on GABA Neurotransmission: The Role of Metabolic Regulatory Points and a Neuronal Glutamate Transporter

Ernesto Solis, Jr.

Neuroscience Graduate Program, Vanderbilt University School of Medicine, U1205 Medical Center North, Nashville, TN 37232, USA.
Correspondence e-mail: ernesto.solis@vanderbilt.edu

Abstract | Full Text | PDF

Abstract | Excessive excitatory drive in the brain is thought to underlie diseases such as epilepsy.  One approach in the development of novel treatments for conditions characterized by hyper-excitability is the enhancement of GABA-mediated inhibition.  While most current medical interventions target GABAergic neurotransmission postsynaptically (e.g. benzodiazepines, barbiturates), much less is known about potential presynaptic therapeutic targets at the GABAergic synapse. This review describes recent findings that have exemplified presynaptic mechanisms that may provide the basis for the development of novel treatments to alter inhibitory neurotransmission.  GABA metabolism is summarized with an emphasis on the role of presynaptic regulatory points in GABA synthesis.  In addition, the excitatory amino acid transporter 3 (EAAT3), which is thought to provide the substrate for GABA synthesis, will be described in detail.  Finally, EAAT3 is presented as a potential therapeutic target to modulate GABA-mediated inhibition presynaptically, and the most recent findings on EAAT3’s functional regulation by several key players are reviewed.